Failure of ureteric bud invasion - A new model of renal agenesis in mice

FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%) . Bilateral renal agenesis is lethal within 2 days after birth. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metane phric mesenchyme at around embryonic day 11, resulting in apoptosis of meta nephric cells and leading to renal agenesis on the affected side. The metan ephros seemed to be normal because co-culturing of the FUBI metanephros wit h homologous spinal cord induced differentiation of the rudiment, but co-cu lturing with the homologous ureteric bud frequently did not. Genetic analys is revealed that more than two genes were involved In this malformation and we mapped one of the modifier loci, fubil, on chromosome 2, at similar to 65 cM from the centromere. In this region, there are two possible candidate genes, Wilms' tumor 1 and formin, that play important roles in kidney deve lopment. Some of formin mutants shared a similar phenotype with FUB1; howev er, there was no difference in the expression of formin in embryonic kidney s between FUB1 and control NFS/N mice. Studies of fubil congenic mice indic ated that interaction of two or more loci is essential for the FUB1 phenoty pe.